The effects of subacute inhaled multi-walled carbon nanotube exposure on signaling pathways associated with cholesterol transport and inflammatory markers in the vasculature of wild-type mice.
The effects of subacute inhaled multi-walled carbon nanotube exposure on signaling pathways associated with cholesterol transport and inflammatory markers in the vasculature of wild-type mice.
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亚急性吸入多壁碳纳米管暴露对野生型小鼠脉管系统中胆固醇转运和炎症标志物相关信号通路的影响。
DOI：
10.1016/j.toxlet.2018.08.004
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发表时间：
2018-10-15
影响因子：
3.5
通讯作者：
Lund AK
中科院分区：
文献类型：
--
作者：
Davis G;Lucero J;Fellers C;McDonald JD;Lund AK
暴露于多壁碳纳米管(MWCNTs)已与有害的心血管后果相关；然而，潜在的机制尚未完全阐明。因此，我们研究了C57BL6/小鼠吸入MWCNTs(1 mg/m~3)或过滤空气(FA-对照组)，每天6小时，14天，导致动脉粥样硬化和促炎信号通路的变化。分析与心血管疾病相关的胆固醇转运介质，即凝集素样氧化型低密度脂蛋白受体-1和三磷酸腺苷结合盒转运蛋白-1、炎症标志物肿瘤坏死因子-α和白介素1β/IL-6、核因子-κB、细胞内/血管黏附分子S(VCAM1)和miRNAs(miR221/−21/−1)的表达。同时检测心肌纤维沉积、基质金属蛋白酶(MMP2/9)和活性氧(ROS)。与FA对照组相比，多壁碳纳米管暴露导致冠脉ROS产生增加，同时LOX-1、血管细胞黏附分子-1、肿瘤坏死因子-α和基质金属蛋白酶-2/9的表达增加，而ABCA-1的表达下调。此外，还观察了心肌纤维化沉积和诱导心肌细胞肿瘤坏死因子-α、基质金属蛋白酶-9、I-κB激酶(IKK)-α/β和miR-221mRNA表达的趋势。使用一氧化氮合酶或NADPH氧化酶抑制剂的分析导致冠状动脉ROS产生减少。这些发现表明，亚急性吸入MWCNT改变了野生型小鼠胆固醇转运体/受体的表达，并诱导了与炎症、氧化应激和心血管疾病相关的信号通路。
Exposure to multi-walled carbon nanotubes (MWCNTs) has been associated with detrimental cardiovascular outcomes; however, underlying mechanisms have not yet been fully elucidated. Thus, we investigated alterations in proatherogenic and proinflammatory signaling pathways in C57Bl6/ mice exposed to MWCNTs (1 mg/m3) or filtered air (FA-Controls), via inhalation, for 6 hr/day, 14d. Expression of mediators of cholesterol transport, namely the lectin-like oxidized low-density lipoprotein receptor (LOX)-1 and ATP-binding cassette transporter (ABCA)-1, inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-κB), intracellular/vascular adhesion molecule(s) (VCAM-1, ICAM-1), and miRNAs (miR-221/−21/−1), associated with cardiovascular disease (CVD), were analyzed in cardiac tissue and coronary vasculature. Cardiac fibrotic deposition, matrix-metalloproteinases (MMP)-2/9, and reactive oxygen species (ROS) were also assessed. MWCNT-exposure resulted in increased coronary ROS production with concurrent increases in expression of LOX-1, VCAM-1, TNF-α, and MMP-2/9 activity; while ABCA-1 expression was downregulated, compared to FA-Controls. Additionally, trends in fibrotic deposition and induction of cardiac TNF-α, MMP-9, IκB Kinase (IKK)-α/β, and miR-221 mRNA expression were observed. Analysis using inhibitors for nitric oxide synthase or NADPH oxidase resulted in attenuated coronary ROS production. These findings suggest that subacute inhalation MWCNT-exposure alters expression of cholesterol transporter/receptors, and induces signaling pathways associated with inflammation, oxidative stress, and CVD in wild-type mice.
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影响因子：
10
作者：
Lee JK;Sayers BC;Chun KS;Lao HC;Shipley-Phillips JK;Bonner JC;Langenbach R
通讯作者：
Langenbach R
由多壁碳纳米管暴露引起的MMP-9依赖性血清传播生物活性通过CD36清道夫受体诱导血管功能障碍。
DOI：
10.1093/toxsci/kfw015
发表时间：
2016-04
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
--
作者：
Aragon M;Erdely A;Bishop L;Salmen R;Weaver J;Liu J;Hall P;Eye T;Kodali V;Zeidler-Erdely P;Stafflinger JE;Ottens AK;Campen MJ
通讯作者：
Campen MJ
影响因子：
39.3
作者：
Akhmedov, Alexander;Rozenberg, Izabela;Luescher, Thomas F.
通讯作者：
Luescher, Thomas F.
影响因子：
--
作者：
Chistiakov DA;Sobenin IA;Orekhov AN;Bobryshev YV
通讯作者：
Bobryshev YV
影响因子：
10
作者：
Dong J;Ma Q
通讯作者：
Ma Q